TY - JOUR
T1 - HMGA1 correlates with advanced tumor grade and decreased survival in pancreatic ductal adenocarcinoma
AU - Hristov, Alexandra C.
AU - Cope, Leslie
AU - Di Cello, Francescopaolo
AU - Reyes, Marcelo Delos
AU - Singh, Mansher
AU - Hillion, Joelle A.
AU - Belton, Amy
AU - Joseph, Biju
AU - Schuldenfrei, Andrew
AU - Iacobuzio-Donahue, Christine A.
AU - Maitra, Anirban
AU - Resar, Linda M.S.
N1 - Funding Information:
Grant support: American Cancer Society Scholar Award, R01 CA092339 and R03 CA139331–01 (L. M. S. Resar), Flight Attendant Medical Research Institute Young Clinical Investigator Award (F. Di Cello), Prevent Cancer Foundation (J. Hillion), Alex’s Lemonade Stand Foundation (L.M.S. Resar and J. Hillion), Joseph C. Eggleston Award (A. Hristov), Maryland Stem Cell Research Fund (L.M.S. Resar, A. Belton, B. Joseph, and J. Hillion), J.P. McCarthy Fund (L.M.S. Resar), and NIH T32 grant (A. Belton).
Funding Information:
The authors kindly thank the generous support of the Joseph C. Eggleston Award and the Eggleston family, the American Cancer Society Scholar Award, Alex’s Lemonade Stand Foundation, the J.P. McCarthy Fund, the Flight Attendant Medical Research Institute Young Clinical Investigator Award, the Prevent Cancer Foundation and the Maryland Stem Cell Research Fund. Also, the authors sincerely thank Dr. Ralph Hruban for his time and contributions to this study.
PY - 2010/1
Y1 - 2010/1
N2 - Although pancreatic ductal adenocarcinoma is a common and almost uniformly fatal cancer, little is known about the molecular events that lead to tumor progression. The high-mobility group A1 (HMGA1) protein is an architectural transcription factor that has been implicated in the pathogenesis and progression of diverse human cancers, including pancreatic ductal adenocarcinoma. In this study, we investigated HMGA1 expression in pancreatic ductal adenocarcinoma cell lines and surgically resected tumors to determine whether it could be a marker for more advanced disease. By real-time quantitative RT-PCR, we measured HMGA1a mRNA in cultured pancreatic ductal adenocarcinoma cell lines and found increased levels in all cancer cells compared with normal pancreatic tissue. To investigate HMGA1 in primary human tumors, we performed immunohistochemical analysis of 125 cases of pancreatic adenocarcinoma and 99 precursor lesions (PanIN 1-3). We found nuclear staining for HMGA1 in 98% of cases of pancreatic adenocarcinoma, but only 43% of cases of PanIN precursor lesions. Moreover, HMGA1 immunoreactivity correlates positively with decreased survival and advanced tumor and PanIN grade. These results suggest that HMGA1 promotes tumor progression in pancreatic ductal adenocarcinoma and could be a useful biomarker and rational therapeutic target in advanced disease.
AB - Although pancreatic ductal adenocarcinoma is a common and almost uniformly fatal cancer, little is known about the molecular events that lead to tumor progression. The high-mobility group A1 (HMGA1) protein is an architectural transcription factor that has been implicated in the pathogenesis and progression of diverse human cancers, including pancreatic ductal adenocarcinoma. In this study, we investigated HMGA1 expression in pancreatic ductal adenocarcinoma cell lines and surgically resected tumors to determine whether it could be a marker for more advanced disease. By real-time quantitative RT-PCR, we measured HMGA1a mRNA in cultured pancreatic ductal adenocarcinoma cell lines and found increased levels in all cancer cells compared with normal pancreatic tissue. To investigate HMGA1 in primary human tumors, we performed immunohistochemical analysis of 125 cases of pancreatic adenocarcinoma and 99 precursor lesions (PanIN 1-3). We found nuclear staining for HMGA1 in 98% of cases of pancreatic adenocarcinoma, but only 43% of cases of PanIN precursor lesions. Moreover, HMGA1 immunoreactivity correlates positively with decreased survival and advanced tumor and PanIN grade. These results suggest that HMGA1 promotes tumor progression in pancreatic ductal adenocarcinoma and could be a useful biomarker and rational therapeutic target in advanced disease.
KW - HMGA1
KW - Immunoreactivity
KW - Oncogene
KW - Pancreatic ductal adenocarcinoma
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U2 - 10.1038/modpathol.2009.139
DO - 10.1038/modpathol.2009.139
M3 - Article
C2 - 19820691
AN - SCOPUS:73949132030
SN - 0893-3952
VL - 23
SP - 98
EP - 104
JO - Modern Pathology
JF - Modern Pathology
IS - 1
ER -